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A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2013
Author Barde Isabelle, Rauwel Benjamin, Marin-Florez Ray Marcel, Corsinotti Andrea, Laurenti Elisa, Verp Sonia, Offner Sandra, Marquis Julien, Kapopoulou Adamandia, Vanicek Jiri, Trono Didier,
Project Innate defenses against retroelements
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Original article (peer-reviewed)

Journal Science (New York, N.Y.)
Volume (Issue) 340(6130)
Page(s) 350 - 3
Title of proceedings Science (New York, N.Y.)
DOI 10.1126/science.1232398


During hematopoiesis, lineage- and stage-specific transcription factors work in concert with chromatin modifiers to direct the differentiation of all blood cells. We explored the role of KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor KAP1 in this process. In mice, hematopoietic-restricted deletion of Kap1 resulted in severe hypoproliferative anemia. Kap1-deleted erythroblasts failed to induce mitophagy-associated genes and retained mitochondria. This was due to persistent expression of microRNAs (miRNAs) targeting mitophagy transcripts, itself secondary to a lack of repression by stage-specific KRAB-ZFPs. The KRAB/KAP1-miRNA regulatory cascade is evolutionarily conserved, as it also controls mitophagy during human erythropoiesis. Thus, a multilayered transcription regulatory system is present, in which protein- and RNA-based repressors are superimposed in combinatorial fashion to govern the timely triggering of an important differentiation event.